The Complete Guide to Antibody-drug Conjugate In Vitro Analysis

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The Complete Guide to Antibody-drug Conjugate
In Vivo Analysis
www.creative-biolabs.com/adc
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Introduction
Chemotherapy is the mainstay of the cancer
standardized treatment program.However, the
nonspecific targeting of healthy cells and tumor
cells by cytotoxic small-molecule drugs often
leads to intolerable side effects, which
compromise the efficacy of the treatment regimen
and dramatically decrease the life quality for
cancer patients. Antibody-drug conjugates (ADCs)
are innovative next-generation immune therapy
agents that combine the specific targeting
capacity of a monoclonal antibody with cytotoxic
drugs. They are designed for accurate drug
delivery to minimize collateral damages to
healthy tissues.
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With the antibody Fc region that triggers
antibody dependent cellular cytotoxicity (ADCC)
or complement dependent cytotoxicity (CDC) and
the cytotoxicity of the ADC payload drug, some
ADCs exert a two-fold killing efficacy towards
targeted cancer cells. Due to their unique
nature, ADC in vivo evaluation is of crucial
importance since this process provides
information regarding their efficacy and safety,
which serves as a prerequisite and a guideline
for clinical trial design.
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Antibody-drug Conjugtae In Vivo Analysis
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ADC Pharmacokinetics Characterization
Pharmacokinetics (PK) studies provide critical
information regarding the behavior of a drug in
circulation and its ultimate form after extensive
in vivo metabolism. Results from PK studies often
serve as guidelines for clinical trials designs,
especially in the development of an antibody-drug
conjugate (ADC). Ideally, the assay methods for
nonclinical PK bioanalysis should be developed
during the early stages of ADC development and
ADC characterization. The evaluation of assays
could be done with the recovery of enriched or
purified drug antibody ratio (DAR) fractions
compared with the average DAR standard to ensure
that the different assay formats recover drug
equally.
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ADC Safety Assessment
The complex nature of antibody-drug conjugates
(ADCs) has raised significant safety concerns.
Each component of an ADC, being the monoclonal
antibody, the small chemical linker, or the toxic
payload drug, contributes uniquely to the overall
ADC toxicity profile in clinical tests, making it
more challenging for ADC assessment evaluate than
that of conventional drugs. Animals that
receive ADCs treatments will be monitored under
Institutional Animal Care and Use Committee
(IACUC) supervision. Basic parameters collected
from clinical observation include body weight,
feed consumption, behavior and pathologic
characteristics. Additional observations such as
ophthalmological feature, urine/Feces, and
respiration also can be conduct as request.
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ADC in vivo Efficacy Evaluation
One important pharmacological parameter of an ADC
is the in vivo efficacy that directly reflects
its potency and influences clinical trial
designs. As an elaborately conjugated entity, the
effector activity residues in the Fc portion of
the monoclonal antibody and the carried cytotoxin
both contribute to the in vivo efficacy of an
ADC, making the assessment more complicated.
After ADC administration in the model animals,
we perform systematic clinical observations to
assess the direct effect of ADCs. The clinical
assessment, including cage-side observation and
clinical check, is conduct by experienced
technicians while physical parameters, such as
body weight, food consumption, and physiological
changes of the tested animals will be recorded
and reported in detail.
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ADC Immunogenicity Analysis
Immunogenicity refers to the development of
adaptive immune responses to therapeutic
biologics. Sometimes, the human immune system
will recognize the therapeutic products and treat
them as hostile immunogenic agents. In the case
of an ADC, anti-drug antibody (ADA) is considered
as one of the major immune responses against
these biologics, thereby increasing the risks for
adverse effect and reducing ADC efficacy. Most
ADCs are generated using human monoclonal
antibodies or humanized antibodies to minimize
immunogenicity and the toxic payloads are usually
not immunogenic. However, as a newly formed
bio-macromolecule, ADCs might present unexpected
immunogenicity, an undesired feature for ADC
performance.
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talented and well-trained scientists located in
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are the established leading expert in TCR and CAR
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entire new drug development pipeline.
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